Neuronal signaling最新文献_第4页

3D hydrogel models of the neurovascular unit to investigate blood-brain barrier dysfunction. 神经血管单元的3D水凝胶模型，用于研究血脑屏障功能障碍。

Neuronal signaling Pub Date : 2021-11-09 eCollection Date: 2021-12-01 DOI: 10.1042/NS20210027

Geoffrey Potjewyd, Katherine A B Kellett, Nigel M Hooper

{"title":"3D hydrogel models of the neurovascular unit to investigate blood-brain barrier dysfunction.","authors":"Geoffrey Potjewyd, Katherine A B Kellett, Nigel M Hooper","doi":"10.1042/NS20210027","DOIUrl":"10.1042/NS20210027","url":null,"abstract":"The neurovascular unit (NVU), consisting of neurons, glial cells, vascular cells (endothelial cells, pericytes and vascular smooth muscle cells (VSMCs)) together with the surrounding extracellular matrix (ECM), is an important interface between the peripheral blood and the brain parenchyma. Disruption of the NVU impacts on blood-brain barrier (BBB) regulation and underlies the development and pathology of multiple neurological disorders, including stroke and Alzheimer's disease (AD). The ability to differentiate induced pluripotent stem cells (iPSCs) into the different cell types of the NVU and incorporate them into physical models provides a reverse engineering approach to generate human NVU models to study BBB function. To recapitulate the in vivo situation such NVU models must also incorporate the ECM to provide a 3D environment with appropriate mechanical and biochemical cues for the cells of the NVU. In this review, we provide an overview of the cells of the NVU and the surrounding ECM, before discussing the characteristics (stiffness, functionality and porosity) required of hydrogels to mimic the ECM when incorporated into in vitro NVU models. We summarise the approaches available to measure BBB functionality and present the techniques in use to develop robust and translatable models of the NVU, including transwell models, hydrogel models, 3D-bioprinting, microfluidic models and organoids. The incorporation of iPSCs either without or with disease-specific genetic mutations into these NVU models provides a platform in which to study normal and disease mechanisms, test BBB permeability to drugs, screen for new therapeutic targets and drugs or to design cell-based therapies.","PeriodicalId":74287,"journal":{"name":"Neuronal signaling","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8579151/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39732931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 14

Super-resolution imaging to reveal the nanostructure of tripartite synapses. 超分辨率成像揭示三方突触的纳米结构

Neuronal signaling Pub Date : 2021-10-14 eCollection Date: 2021-12-01 DOI: 10.1042/NS20210003

Natalija Aleksejenko, Janosch P Heller

{"title":"Super-resolution imaging to reveal the nanostructure of tripartite synapses.","authors":"Natalija Aleksejenko, Janosch P Heller","doi":"10.1042/NS20210003","DOIUrl":"10.1042/NS20210003","url":null,"abstract":"Even though neurons are the main drivers of information processing in the brain and spinal cord, other cell types are important to mediate adequate flow of information. These include electrically passive glial cells such as microglia and astrocytes, which recently emerged as active partners facilitating proper signal transduction. In disease, these cells undergo pathophysiological changes that propel disease progression and change synaptic connections and signal transmission. In the healthy brain, astrocytic processes contact pre- and postsynaptic structures. These processes can be nanoscopic, and therefore only electron microscopy has been able to reveal their structure and morphology. However, electron microscopy is not suitable in revealing dynamic changes, and it is labour- and time-intensive. The dawn of super-resolution microscopy, techniques that 'break' the diffraction limit of conventional light microscopy, over the last decades has enabled researchers to reveal the nanoscopic synaptic environment. In this review, we highlight and discuss recent advances in our understanding of the nano-world of the so-called tripartite synapses, the relationship between pre- and postsynapse as well as astrocytic processes. Overall, novel super-resolution microscopy methods are needed to fully illuminate the intimate relationship between glia and neuronal cells that underlies signal transduction in the brain and that might be affected in diseases such as Alzheimer's disease and epilepsy.","PeriodicalId":74287,"journal":{"name":"Neuronal signaling","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8536832/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39680469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Conventional protein kinase C in the brain: repurposing cancer drugs for neurodegenerative treatment? 脑中的常规蛋白激酶 C：重新利用抗癌药物治疗神经退行性疾病？

Neuronal signaling Pub Date : 2021-10-08 eCollection Date: 2021-12-01 DOI: 10.1042/NS20210036

Gema Lordén, Alexandra C Newton

引用次数: 0

A sticky situation: regulation and function of protein palmitoylation with a spotlight on the axon and axon initial segment. 棘手的情况：蛋白质棕榈酰化的调节和功能，重点关注轴突和轴突起始段。

Neuronal signaling Pub Date : 2021-10-06 eCollection Date: 2021-12-01 DOI: 10.1042/NS20210005

Andrey A Petropavlovskiy, Jordan A Kogut, Arshia Leekha, Charlotte A Townsend, Shaun S Sanders

{"title":"A sticky situation: regulation and function of protein palmitoylation with a spotlight on the axon and axon initial segment.","authors":"Andrey A Petropavlovskiy, Jordan A Kogut, Arshia Leekha, Charlotte A Townsend, Shaun S Sanders","doi":"10.1042/NS20210005","DOIUrl":"10.1042/NS20210005","url":null,"abstract":"In neurons, the axon and axon initial segment (AIS) are critical structures for action potential initiation and propagation. Their formation and function rely on tight compartmentalisation, a process where specific proteins are trafficked to and retained at distinct subcellular locations. One mechanism which regulates protein trafficking and association with lipid membranes is the modification of protein cysteine residues with the 16-carbon palmitic acid, known as S-acylation or palmitoylation. Palmitoylation, akin to phosphorylation, is reversible, with palmitate cycling being mediated by substrate-specific enzymes. Palmitoylation is well-known to be highly prevalent among neuronal proteins and is well studied in the context of the synapse. Comparatively, how palmitoylation regulates trafficking and clustering of axonal and AIS proteins remains less understood. This review provides an overview of the current understanding of the biochemical regulation of palmitoylation, its involvement in various neurological diseases, and the most up-to-date perspective on axonal palmitoylation. Through a palmitoylation analysis of the AIS proteome, we also report that an overwhelming proportion of AIS proteins are likely palmitoylated. Overall, our review and analysis confirm a central role for palmitoylation in the formation and function of the axon and AIS and provide a resource for further exploration of palmitoylation-dependent protein targeting to and function at the AIS.","PeriodicalId":74287,"journal":{"name":"Neuronal signaling","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8495546/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39526158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4

The immunogenicity of midbrain dopaminergic neurons and the implications for neural grafting trials in Parkinson's disease. 中脑多巴胺能神经元的免疫原性及其对帕金森病神经移植试验的影响。

Neuronal signaling Pub Date : 2021-09-13 eCollection Date: 2021-09-01 DOI: 10.1042/NS20200083

Shamma Qarin, Sarah K Howlett, Joanne L Jones, Roger A Barker

引用次数: 1

Cannabidiol modulation of oxidative stress and signalling. 大麻二酚调节氧化应激和信号传导。

Neuronal signaling Pub Date : 2021-08-24 eCollection Date: 2021-09-01 DOI: 10.1042/NS20200080

Sónia R Pereira, Becky Hackett, David N O'Driscoll, Melody Cui Sun, Eric J Downer

{"title":"Cannabidiol modulation of oxidative stress and signalling.","authors":"Sónia R Pereira, Becky Hackett, David N O'Driscoll, Melody Cui Sun, Eric J Downer","doi":"10.1042/NS20200080","DOIUrl":"https://doi.org/10.1042/NS20200080","url":null,"abstract":"Cannabidiol (CBD), one of the primary non-euphoric components in the Cannabis sativa L. plant, has undergone clinical development over the last number of years as a therapeutic for patients with Lennox-Gastaut syndrome and Dravet syndromes. This phytocannabinoid demonstrates functional and pharmacological diversity, and research data indicate that CBD is a comparable antioxidant to common antioxidants. This review gathers the latest knowledge regarding the impact of CBD on oxidative signalling, with focus on the proclivity of CBD to regulate antioxidants and control the production of reactive oxygen species. CBD is considered an attractive therapeutic agent for neuroimmune disorders, and a body of literature indicates that CBD can regulate redox function at multiple levels, with a range of downstream effects on cells and tissues. However, pro-oxidant capacity of CBD has also been reported, and hence caution must be applied when considering CBD from a therapeutic standpoint. Such pro- and antioxidant functions of CBD may be cell- and model-dependent and may also be influenced by CBD dose, the duration of CBD treatment and the underlying pathology.","PeriodicalId":74287,"journal":{"name":"Neuronal signaling","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8385185/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39414754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 24

Anti-inflammatory cytokine-eluting collagen hydrogel reduces the host immune response to dopaminergic cell transplants in a rat model of Parkinson's disease. 抗炎细胞因子洗脱胶原水凝胶降低帕金森病大鼠模型中多巴胺能细胞移植的宿主免疫反应。

Neuronal signaling Pub Date : 2021-08-23 eCollection Date: 2021-09-01 DOI: 10.1042/NS20210028

Sílvia Cabré, Verónica Alamilla, Niamh Moriarty, Abhay Pandit, Eilís Dowd

{"title":"Anti-inflammatory cytokine-eluting collagen hydrogel reduces the host immune response to dopaminergic cell transplants in a rat model of Parkinson's disease.","authors":"Sílvia Cabré, Verónica Alamilla, Niamh Moriarty, Abhay Pandit, Eilís Dowd","doi":"10.1042/NS20210028","DOIUrl":"https://doi.org/10.1042/NS20210028","url":null,"abstract":"In cell replacement approaches for Parkinson's disease, the intracerebral implantation of dopamine neuron-rich grafts generates a neuroinflammatory response to the grafted cells that contributes to its varied outcome. Thus, the aim of the present study was to fabricate an anti-inflammatory cytokine-eluting collagen hydrogel capable of delivering interleukin (IL)-10 to the brain for reduction of the neuroinflammatory response to intracerebral cellular grafts. In vitro assessment revealed that cross-linker concentration affected the microstructure and gelation kinetics of the hydrogels and their IL-10 elution kinetics, but not their cytocompatibility or the functionality of the eluted IL-10. In vivo evaluation revealed that the hydrogels were capable of delivering and retaining IL-10 in the rat striatum, and reducing the neuroinflammatory (microglial) response to hydrogel-encapsulated grafts. In conclusion, IL-10-eluting collagen hydrogels may have beneficial anti-inflammatory effects in the context of cellular brain repair therapies for Parkinson's disease and should be investigated further.","PeriodicalId":74287,"journal":{"name":"Neuronal signaling","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8385187/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39397180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Oligodendrocytes in the aging brain. 衰老大脑中的少突胶质细胞。

Neuronal signaling Pub Date : 2021-07-06 eCollection Date: 2021-09-01 DOI: 10.1042/NS20210008

Eleanor Catherine Sams

{"title":"Oligodendrocytes in the aging brain.","authors":"Eleanor Catherine Sams","doi":"10.1042/NS20210008","DOIUrl":"10.1042/NS20210008","url":null,"abstract":"More than half of the human brain volume is made up of white matter: regions where axons are coated in myelin, which primarily functions to increase the conduction speed of axon potentials. White matter volume significantly decreases with age, correlating with cognitive decline. Much research in the field of non-pathological brain aging mechanisms has taken a neuron-centric approach, with relatively little attention paid to other neural cells. This review discusses white matter changes, with focus on oligodendrocyte lineage cells and their ability to produce and maintain myelin to support normal brain homoeostasis. Improved understanding of intrinsic cellular changes, general senescence mechanisms, intercellular interactions and alterations in extracellular environment which occur with aging and impact oligodendrocyte cells is paramount. This may lead to strategies to support oligodendrocytes in aging, for example by supporting myelin synthesis, protecting against oxidative stress and promoting the rejuvenation of the intrinsic regenerative potential of progenitor cells. Ultimately, this will enable the protection of white matter integrity thus protecting cognitive function into the later years of life.","PeriodicalId":74287,"journal":{"name":"Neuronal signaling","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8264650/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39206890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 28

α-synuclein pathogenesis in hiPSC models of Parkinson's disease. α-突触核蛋白在帕金森病hiPSC模型中的发病机制。

Neuronal signaling Pub Date : 2021-06-23 eCollection Date: 2021-06-01 DOI: 10.1042/NS20210021

Jara M Baena-Montes, Sahar Avazzadeh, Leo R Quinlan

{"title":"α-synuclein pathogenesis in hiPSC models of Parkinson's disease.","authors":"Jara M Baena-Montes, Sahar Avazzadeh, Leo R Quinlan","doi":"10.1042/NS20210021","DOIUrl":"https://doi.org/10.1042/NS20210021","url":null,"abstract":"α-synuclein is an increasingly prominent player in the pathology of a variety of neurodegenerative conditions. Parkinson's disease (PD) is a neurodegenerative disorder that affects mainly the dopaminergic (DA) neurons in the substantia nigra of the brain. Typical of PD pathology is the finding of protein aggregations termed 'Lewy bodies' in the brain regions affected. α-synuclein is implicated in many disease states including dementia with Lewy bodies (DLB) and Alzheimer's disease. However, PD is the most common synucleinopathy and continues to be a significant focus of PD research in terms of the α-synuclein Lewy body pathology. Mutations in several genes are associated with PD development including SNCA, which encodes α-synuclein. A variety of model systems have been employed to study α-synuclein physiology and pathophysiology in an attempt to relate more closely to PD pathology. These models include cellular and animal system exploring transgenic technologies, viral vector expression and knockdown approaches, and models to study the potential prion protein-like effects of α-synuclein. The current review focuses on human induced pluripotent stem cell (iPSC) models with a specific focus on mutations or multiplications of the SNCA gene. iPSCs are a rapidly evolving technology with huge promise in the study of normal physiology and disease modeling in vitro. The ability to maintain a patient's genetic background and replicate similar cell phenotypes make iPSCs a powerful tool in the study of neurological diseases. This review focuses on the current knowledge about α-synuclein physiological function as well as its role in PD pathogenesis based on human iPSC models.","PeriodicalId":74287,"journal":{"name":"Neuronal signaling","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8222967/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39165998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5

Exploiting the neuroprotective effects of α-klotho to tackle ageing- and neurodegeneration-related cognitive dysfunction. 利用α-klotho的神经保护作用来解决衰老和神经退行性相关的认知功能障碍。

Neuronal signaling Pub Date : 2021-06-14 eCollection Date: 2021-06-01 DOI: 10.1042/NS20200101

Kelsey Hanson, Kate Fisher, Nigel M Hooper

{"title":"Exploiting the neuroprotective effects of α-klotho to tackle ageing- and neurodegeneration-related cognitive dysfunction.","authors":"Kelsey Hanson, Kate Fisher, Nigel M Hooper","doi":"10.1042/NS20200101","DOIUrl":"10.1042/NS20200101","url":null,"abstract":"Cognitive dysfunction is a key symptom of ageing and neurodegenerative disorders, such as Alzheimer's disease (AD). Strategies to enhance cognition would impact the quality of life for a significant proportion of the ageing population. The α-klotho protein may protect against cognitive decline through multiple mechanisms: such as promoting optimal synaptic function via activation of N-methyl-d-aspartate (NMDA) receptor signalling; stimulating the antioxidant defence system; reducing inflammation; promoting autophagy and enhancing clearance of amyloid-β. However, the molecular and cellular pathways by which α-klotho mediates these neuroprotective functions have yet to be fully elucidated. Key questions remain unanswered: which form of α-klotho (transmembrane, soluble or secreted) mediates its cognitive enhancing properties; what is the neuronal receptor for α-klotho and which signalling pathways are activated by α-klotho in the brain to enhance cognition; how does peripherally administered α-klotho mediate neuroprotection; and what is the molecular basis for the beneficial effect of the VS variant of α-klotho? In this review, we summarise the recent research on neuronal α-klotho and discuss how the neuroprotective properties of α-klotho could be exploited to tackle age- and neurodegeneration-associated cognitive dysfunction.","PeriodicalId":74287,"journal":{"name":"Neuronal signaling","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8204227/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39127276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 10